IB BIOLOGY Option A.5 Neuropharmacology

Interactions at the Synapse Action potential causes flood of Ca2+ ions release of NT at cleft

Excitatory and Inhibitory NTs Ach-excitatory NT generates AP Increase permeability of post-synaptic neuron to + ions Na+ floods in  depolarizedAP GABA- inhibitory NT Inhibits AP Cause hyperpolarization harder for AP to be generated Binds to receptor Cl- move in neuron or K+ to move out of post synaptic neuron

Modulation of Synaptic Transmission Fast acting NTs: Affect target cell in 1 millisecond of binding to receptor Ex: Glutamate, GABA Slow acting NTs: Affect target cell in hundreds of milliseconds or up to a minute Act on second messenger molecule, more time consuming Neuromodulators Released in CSF modulate FA NTs Regulate efficiency of NT release Regulate efficiency of receptor Ex: dopamine, serotonin, acetylcholine

Memory and Learning FA and SA NTs affect learning and memory. Experiment with Aplysia: pg 548 Short term process (learning) vs. long term process (memory) Long term needs synthesis of proteins Proteins change form and function of synapse memory Stronger, long lasting stimulus needed for long term

Cholinergic Receptors Receptors for Ach- excitatory NT Part of parasympathetic NS (business as usual) Acetylcholine esterase breaks down Ach after release at synapse to keep neuron from continually firing Nicotine binds to these receptors

Adrenergic Receptors Receptors for Noradrenaline Part of parasympathetic NS- (fight or flight) Cocaine and amphetamines affect this receptor

Excitatory Drugs (Stimulants) Cocaine, amphetamines, MDMA Increase nerve transmission

Inhibitory Drugs (Sedatives) Alcohol, THC, benzodiazepines, opiates Decrease nerve transmission

Drugs can act on synapses by: 1. Blocking a receptor for an NT 2. Blocking release of an NT 3. Enhancing release of an NT 4. Enhancing an NT by mimicking an NT (analog) 5. Blocking removal of an NT, thus enhancing its effect.

Excitatory Drugs Nicotine Mimics Ach, attaches and changes the cholinergic receptor Ach is normally broken down in synapse by Ach esterase, but body cannot break down nicotine Nicotine excites post-synaptic neuron to release Dopamine(Da), causing feelings of pleasure.

Excitatory drugs, cont. Cocaine Stimulates transmission at adrenergic receptors Increases alertness, euphoria Also increases release of Da Blocks removal of Da, which causes build-up and overstimulation of post-synaptic neuron Increases feelings of reward and euphoria

Excitatory drugs, cont. Amphetamine Stimulates transmission at adrenergic synapses increasing alertness and euphoria Passes directly into the nerve cells, which carry DA and NA, moves DA and NA vesicles of pre-synaptic neuron for release in the synaptic cleft. DA and NA normally removed by enzymes, but amphetamine interferes with this process Result- more alertness and more euphoria

Excitatory drugs, cont. MDMA Structurally related to amphetamines Causes extra release of serotonin (Se) Cell bodies of Se neurons are in brainstem and have an axon network in the brain

Excitatory drugs, cont. MDMA mechanism of action- Presynaptic neuron releases Se Receptor of postsynaptic neuron activated by Se A SERT (Se transport) vesicle on presynaptic neuron takes up extra Se MDMA forces Se axons to release a lot of Se When SERT catches up depression results Se levels can become depleted

Excitatory drugs, cont. MDMA and Dopamine Se depleted, SERT receptor is empty DA enters SERT receptor by mistake DA broken down, products are toxic to Se producing neurons Neurotoxicity causes long-term brain cell damage https://www.youtube.com/watch?v=jEAr7ThsYew

Inhibitory Drugs Benzodiazepines Ex. Valium, used for seizures in epileptics Modulate GABA GABA binds to postsynaptic neuron causing Cl- to enter, result is hyperpolarization of neuron Increase binding of GABA, increasing inhibitory signals

Inhibitory drugs, cont. Alcohol Increased binding of GABA to postsynaptic neuron Decreases activity of glutamate, an excitatory NT Overall sedative effect results Increases the release of DA, and stops activity that breaks down DA at synapse Affects cerebellum coordination and reflexes Affects the limbic system memory

https://www.youtube.com/watch?v=zXjANz9r5F0

Inhibitory drugs, cont. THC (tetrahydrocannabinol) Main psychoactive ingredient in marijuana Mimics anandamide, NT involved with memory Binds to cannabinoid receptors hyperpolarizes neurons Body breaks down anandamide, but not THC Disrupts short term memory in humans “relaxed and mellow” feelings, also paranoia and panic Dilates pupils Problems with learning, memory, coordination, problem solving

https://dotsub.com/view/d5638865-f253-4f11-9928-763ee68abbcc

Anesthetics: Used by doctors and dentists Novocain- local anesthetic Blocks nerve transmission to pain centers Na+ rushes in neurons pain felt Block Na+ no pain Drug induced insensitivity

https://www.youtube.com/watch?v=r-0Mg9FNchc

Anesthetics, cont. General anesthesia- Modifies function of gated ion channels Binds directly to ion channels Synaptic block: Reduces presynaptic Ca2+ entry, reducing NT release Increases postsynaptic Cl- entry and increases outward K+ Conduction block: Reduces axonal Na+ entry which results in failure of AP propagation

Endorphins Discovered while studying opium addiction Receptors for heroin, morphine and other opiates in brain cells Endorphins are CNS NTs that have pain relieving properties. Released by pituitary gland during stress, injury or exercise Small peptides that bind to opiate receptors Block transmission of pain impulses Bind to receptors of neurons involved with pain perceptionblock release of NTs

Addiction Addictive drugs: Body develops tolerance: Addiction is: Alcohol, tobacco, psychoactive drugs, pharmaceuticals Take to alleviate symptoms: Mental illness or for pleasure Body develops tolerance: Needs more drugs to produce desired effects. Addiction is: Chemical dependency on drugs where the drug has “re-wired” the brain so that it becomes an essential biochemical for the body

Addiction Series https://www.youtube.com/watch?v=wxiKVQR90VM&list=PLA8F89537FD4C3FD1 https://www.youtube.com/watch?v=ekDFv7TTZ4I&index=2&list=PLA8F89537FD4C3FD1 https://www.youtube.com/watch?v=u_scpXuE4rk&index=3&list=PLA8F89537FD4C3FD1 https://www.youtube.com/watch?v=kVoYpiiy7jg&list=PLA8F89537FD4C3FD1&index=4

https://www. youtube. com/watch https://www.youtube.com/watch?v=op0XqgWQn7E&index=5&list=PLA8F89537FD4C3FD1 https://www.youtube.com/watch?v=jkOl7QIXxlQ&index=6&list=PLA8F89537FD4C3FD1 https://www.youtube.com/watch?v=rAx_WB0VVho&index=7&list=PLA8F89537FD4C3FD1 https://www.youtube.com/watch?v=QR0rneaFego&list=PLA8F89537FD4C3FD1&index=8

Withdrawal Symptoms opposite of euphoria Alcohol withdrawal: Anxiety, depression and cravings Alcohol withdrawal: Seizures and delerium tremens (shaking) Can be fatal Inhaled drugs damage lung tissue Kidney disease can develop High risk behaviors: Sharing needles Unprotected sexual relations Risk for HIV, hepatitis B and C

Genetic Predisposition Twin studies: Identical twins- 100% genetically identical Fraternal twins- 50% genetically identical Male twin studies give support to genetic component Rats Genetically manipulated to prefer alcohol Had 20% lower dopamine levels Non-alcohol rats consumed far less ethanol in studies

Social Factors Family of child Parenting skills Mental health of family members Peer pressure: High in adolescents, lower in adults Users teach new users Introducing new drug into culture British opium into China- disaster Heroin-disaster for US Saudi Arabia forbids alcohol, so its not a social problem there Addiction more likely if drugs are cheap and easily available

Dopamine Secretion Addiction: More of drug is needed to feel “normal” Dopamine receptors constantly being stimulated Decreases the number of receptors Receptors that remain become desensitized: tolerance More of drug is needed to feel “normal” Neuroadaptive change produces addiction Glutamate: oversees the learning and memories that lead to drug seeking behaviors